Electrical impedance myography (EIM) is a new, safe, non-invasive, and rapidly applied technique for muscle assessment that we have been developing in our laboratory for the past several years. In EIM, low- intensity alternating current of varying frequencies is passed through muscle tissue and the consequent surface voltage patterns assessed. The technique holds the promise of assisting with the diagnosis and assessment of many conditions that produce muscle atrophy and weakness, including muscular dystrophies, neurogenic illnesses (such as amyotrophic lateral sclerosis), inflammatory myopathies, disuse states, and muscle wasting of the elderly. Our current work in normal human subjects and those with a variety of neuromuscular disorders is confirming the potential value of this methodology. However, many questions remain regarding the nature of the measurements and their specific relationship with muscle pathology. In this proposal, we address these questions by performing detailed EIM measurements in rat models of neuromuscular disease and obtaining quantitative histomorphometry on the muscle tissue. Our first aim will focus on further refining the technique for use in rats, confirming its reproducibility and identifying changes in EIM parameters with normal rat growth and aging. The second aim will study a neurogenic disease model by following changes in muscle pathology and EIM measurements with degeneration and recovery from a nerve crush injury. The third aim will evaluate the correlation between EIM measures in a model of inflammatory myositis. The fourth aim will study muscle pathology and impedance change due to disuse using a hind limb suspension model. With these data, our current network models of underlying EIM theory will be further refined with the aim of being able to predict accurately muscle pathology from the EIM data. Additional outcomes of this work include: 1. learning how EIM parameters change with growth and aging;2. improving our ability to work with small muscles such that EIM can be used more effectively in children with muscular dystrophy and other disorders, and 3. to prepare the way for the use of EIM in screening of drugs and therapies in animals models of neuromuscular disease.